LECTURE 6 - GENE FUNCTIONS: PROTEINS AND ENZYMES

Archibald Garrod

inborn errors of metabolism

first evidence of specific relationship between gene and enzymes

Alkaptonuria

HA oxidase malfunction

accumulation of HA results to oxidation forming black urine when exposed to air

Cretinism

Iodotyrosine deiodinase

physical deformity and learning disabilities

Galactosemia

Gal 1 p uridyl transferase

liver enlargement, galactose in blood

Huntington's disease

Glutamic acid decarboxylase

progressive mental retardation

Jaundice

Glucoronyl transferase

presence of bile in various tissues

Lesch-Nyhan syndrome

Hypoxanthine-guanine phosphoribosyltransferase

Mental retardation, self mutilation

Phenylketonuria (PKU)

phenylalanine hydroxylase

Mental retardation, excretion of phenylalanine

Tay-Sachs disease

B-N-D acetyl hexosaminidase

mental and motor retardation

albinism

tyrosinase

no melanin pigments in the hair, skin eyes

george beadle and edward tatum

one gene-one enzyme hypothesis

one gene-one protein

one gene-one polypeptide

pribnow box

-10 promoter site (prokaryotic)

goldberg-hogness box

-25 to -30 promoter site (eukaryotic)

RNA Polymerase I

large tRNAs

RNA polymerase II

mRNA

RNA polymerase III

transcribes tRNA and some other small nuclear RNAs

George Gamow

proposed the need for a genetic coding system

Grunberg-Manago and Ochoa

made synthetic RNAs using polynucleotide phosphorylase

_TP would yield to _

Nirenberg and Matthaei

produced artificial mRNA and introduced into a cell free system

Francis Crick and his students

1. code for several amino acids

2. genetic code is triplet (4^3 = 64>>20 amino acids)

3. one amino acid can be coded by more than one codon

4. code is not overlapping

Khorana

constructed synthetic mRNA with different repeating nucleotide combinations

Colinearity of a Gene and Protein

The linear sequence of nucleotides in a gene determines the linear sequence of amino acids in a protein.

Yanofsky et al., 1964

Found that mutations in a certain DNA position affected the corresponding amino acid in the protein

21st amino acid - Selenocysteine

UGA usually means stop, but sometimes it says 'insert selenocysteine

22nd amino acid - Pyrrolysine

Another stop codon can be redefined to code a special amino acid in certain microbes

Eukaryotic pre-mRNA

DNA → Pre-mRNA → (5' cap + splicing + poly-A tail) → Mature mRNA → Translation

special transfers

RNA replication

Reverse transcription

gene regulation

ability of cell to determine:

1. which genes should be expressed

2. when those genes should be expressed

3. how much of gene product

regulated genes

expressed only when needed

constitutive or housekeeping genes

- constantly being transcribed

- expressed all the time

- gene products are essential for maintenance

two types of operons

Lactose/inducible operon

Trptophan/repressible operon

lac operon

system usually OFF when no lactose is present

trp operon

system usually ON when tryptophan level is low